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BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-β, Favoring Th2 and Foxp3+ Treg Polarization.
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2020-03-31 , DOI: 10.3389/fimmu.2020.00518
Jun-Ai Zhang 1, 2 , Yuan-Bin Lu 1, 2 , Wan-Dang Wang 1, 3 , Gan-Bin Liu 4 , Chen Chen 1, 2 , Ling Shen 5 , Hou-Long Luo 1, 2 , Huan Xu 1, 2 , Ying Peng 1, 2 , Hong Luo 1, 2 , Gui-Xian Huang 1, 2 , Du-Du Wu 6 , Bi-Ying Zheng 2 , Lai-Long Yi 4 , Zheng W Chen 5 , Jun-Fa Xu 1, 2
Affiliation  

Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs. Active TB patients exhibited higher expression of BTLA in myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) subsets compared with healthy controls (HCs). BTLA expression was similarly high in untreated TB, TB relapse, and sputum-bacillus positive TB, but anti-TB therapy reduced TB-driven increases in frequencies of BTLA+ DCs. BTLA+ DCs in active TB showed decreased expression of the DC maturation marker CD83, with an increased expression of CCR7 in mDCs. BTLA+ DCs in active TB displayed a decreased ability to express HLA-DR and to uptake foreign antigen, with a reduced expression of the co-stimulatory molecule CD80, but not CD86. Functionally, BTLA+ DCs in active TB showed a decreased production of IL-12 and IFN-α as well as a reduced ability to stimulate allogeneic T-cell proliferative responses. BTLA+ mDCs produced larger amounts of IL-4 and TGF-β than BTLA- mDCs in both HCs and APT patients. BTLA+ DCs from active TB patients showed a reduced ability to stimulate Mtb antigen-driven Th17 and Th22 polarizations as compared to those from HCs. Conversely, these BTLA+ DCs more readily promoted the differentiation of T regulatory cells (Treg) and Th2 than those from HCs. These findings suggest that TB-driven BTLA expression in DCs impairs the expression of functional DC surrogate markers and suppress the ability of DCs to induce anti-TB Th17 and Th22 response while promoting Th2 and Foxp3+ Tregs.

中文翻译:

结核患者中表达BTLA的树突状细胞表现出IL-12 /IFN-α减少,IL-4和TGF-β产生增加,有利于Th2和Foxp3 + Treg极化。

关于结核病(TB)如何损害树突状细胞(DC)功能和抗结核病免疫反应知之甚少。我们先前显示B和T淋巴细胞减毒剂(BTLA),一种免疫抑制受体,参与了TB的发病机理。在这里,我们检查了结核中的BTLA表达是否影响DC的表型和功能方面。与健康对照组(HCs)相比,活跃的TB患者在髓样树突状细胞(mDCs)和浆细胞样DC(pDCs)亚组中表现出更高的BTLA表达。在未经治疗的结核病,结核病复发和痰杆菌阳性结核病中,BTLA表达同样较高,但是抗结核病治疗减少了由TB驱动的BTLA + DC频率增加。活动性TB中的BTLA + DC显示出DC成熟标志物CD83的表达减少,而在mDC中CCR7的表达增加。活动性TB中的BTLA + DC表现出降低的表达HLA-DR和摄取外源抗原的能力,同时共刺激分子CD80而不是CD86的表达降低。从功能上讲,活动性结核病中的BTLA + DC表现出IL-12和IFN-α降低的产生,以及刺激同种异体T细胞增殖反应的能力降低。在HCs和APT患者中,BTLA + mDC比BTLA-mDC产生更多的IL-4和TGF-β。与来自HCs的患者相比,来自活动性TB患者的BTLA + DCs刺激Mtb抗原驱动的Th17和Th22极化的能力降低。相反,与HCs相比,这些BTLA + DC更容易促进T调节细胞(Treg)和Th2的分化。
更新日期:2020-03-31
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